Patients with systemic lupus erythematosus show increased platelet activation and endothelial dysfunction induced by acute hyperhomocysteinemia.

Abstract

Hyperhomocysteinemia adversely affects the endothelium, although the exact mechanism is unclear. Systemic lupus erythematosus (SLE) is an inflammatory disease with a high atherothrombotic tendency. We examined whether acute hyperhomocysteinemia exacerbates endothelial and platelet dysfunction in patients with SLE. Twelve SLE patients and 15 controls were recruited. Oral methionine was used to achieve acute hyperhomocysteinemia. Endothelial function was assessed by flow-mediated dilatation (FMD) of the brachial artery; also assessed were the levels of von Willebrand factor (vWF) and plasminogen activator inhibitor type 1 (PAI-1). Platelet activation was assessed by the levels of beta-thromboglobulin (beta-TG), fibrinogen binding, and P-selectin expression using flow cytometry. After oral methionine loading, vWF levels increased significantly, whereas FMD remained unchanged in both groups. PAI-1 increased significantly only in controls. Fibrinogen binding to platelets increased significantly only in SLE patients. Beta-TG remained unchanged in SLE patients but increased significantly in controls. Platelet P-selectin expression did not change in either group. These results suggest that the prothrombotic tendency after acute hyperhomocysteinemia is mediated by endothelial dysfunction and platelet activation in patients with SLE and healthy controls.